Chronic infection by intracellular pathogens commonly fails to elicit neutralizing antibody responses. In Science Immunology, three studies by McGavern, Pinschewer and Iannacone and their colleagues report how humoral immunity is blunted during chronic infection with lymphocytic choriomeningitis virus. All three studies invoke early loss of virus-specific B cells dependent on interferon-α and interferon-β (IFN-α/β), which thereby indirectly blunts the generation of neutralizing antibodies. Blockade of the IFN-α/β receptor 'rescues' B cell loss. The studies differ on how IFN-α/β signaling triggers such loss; however, suggested roles include activated CD8+ T cells, nitric-oxide production by CCR2+ inflammatory monocytes, and production of the cytokine TNF by myeloid cells within infected lymph nodes. Curiously, this inhibitory effect wanes within 3–6 d of infection, which suggests a temporal window for boosting the production of neutralizing antibodies by inhibiting IFN-α/β signaling.

Sci. Immunol. 1, eaah3565, eaah6817 & eaah6789 (21 October 2016)